INDUCTION OF TISSUE TRANSGLUTAMINASE BY DYNAMIC LOAD

通过动态负载诱导组织转谷氨酰胺酶

• 批准号: 6420030
• 负责人: RONALD DAVID GRAFF
• 金额: $ 0.34万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-10-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6420030
• 关键词: chondrocytes; crosslink; enzyme induction /repression; extracellular matrix proteins; immunocytochemistry; in situ hybridization; mechanical pressure; molecular film; polymerase chain reaction; protein glutamine gamma glutamyltransferase; tissue /cell culture

The objective of this proposal is to further our understanding of the mechanisms by which chondrocytes respond to dynamic mechanical load. Tissue transglutaminase (tTG) stabilizes extracellular matrix of many tissues, including cartilage, via the cross-linking of proteins such as fibronectin and collagen and may be important for the strengthening or remodeling of cartilage matrix in response to dynamic load. Furthermore, disruption of normal tTG functioning may contribute to the development or progression of osteoarthritis. The aims of this proposal are: l) to examine by immunocytochemistry and in situ hybridization the expression and localization of tTG in chondron pellet cultures before and after cyclic compressive loading; 2) to measure the cross-linking activity of tTG in response to cyclic compressive loading in chondron pellet cultures by examining the incorporation of exogenous tTG substrates; 3) to identify immunologically the endogenous matrix proteins which are cross-linked by tTG in loaded chondron pellets, and determine the pattern of cross-linking induced by loads of different strengths. These studies will provide a clearer understanding of the role of tTG in articular cartilage.

该提案的目的是进一步了解软骨细胞响应动态机械负荷的机制。组织转谷氨酰胺酶 (tTG) 通过纤连蛋白和胶原蛋白等蛋白质的交联来稳定包括软骨在内的许多组织的细胞外基质，并且对于响应动态负载而增强或重塑软骨基质可能很重要。此外，正常 tTG 功能的破坏可能会导致骨关节炎的发生或进展。本提案的目的是： l) 通过免疫细胞化学和原位杂交检查循环压缩加载前后软骨颗粒培养物中 tTG 的表达和定位； 2) 通过检查外源 tTG 底物的掺入情况，测量 tTG 响应软骨颗粒培养物中循环压缩载荷的交联活性； 3)免疫学鉴定负载软骨颗粒中通过tTG交联的内源性基质蛋白，并确定不同强度负载诱导的交联模式。这些研究将使人们更清楚地了解 tTG 在关节软骨中的作用。